The present invention relates to a process for producing 1-.beta.-D-arabinofuranosylcytosine-5'-stearylphosphate monosodium salt which is excellent in stability and 1-.beta.-D-arabinofuranosylcytosine-5'-stearylphosphate monosodium salt monohydrate which is nonhygroscopic and is excellent in stability.
A process for producing 1-.beta.-D-arabinofuranosylcytosine-5'-stearylphosphate sodium (hereinafter referred to as Ara-C-5'-stearylphosphate sodium salt) has been disclosed in Japanese Patent Publication No. 55-49588 (1980). According to the disclosed process, after adjusting an aqueous solution of Ara-C-5'-stearylphosphate (a free acid) to pH of 7.0 by sodium hydroxide, the thus adjusted aqueous solution is condensed and ethanol was added to the condensate, thereby precipitating Ara-C-5'-stearylphosphate sodium salt.
Ara-C-5'-stearylphosphate sodium salt obtained by the process disclosed in Japanese Patent Publication No. 55-49588 (1980) is a powdery substance and does not show any definite diffraction peaks on X-ray diffraction, namely, it is an amorphous substance (refer to FIG. 3).
In the case where Ara-C-5'-stearylphosphate sodium salt obtained by the above conventional process was left for 14 months under the conditions of a temperature of 25.degree. C. and a relative humidity (RH) of 75%, the content thereof was reduced to 93.7% by weight of the initial value and in the case where left for 3 months under the conditions of a temperature of 50.degree. C. and an RH of 74%, the content thereof was remarkably reduced to 58.6% by weight of the initial value, and it was ascertained that 1-.beta.-D-arabinofuranosyluracil-5'-stearylphosphate sodium salt was formed as a decomposition product.
Furthermore, in the case where Ara-C-5'-stearylphosphate sodium salt was left under the condition of a temperature of 25.degree. C. and an RH of 93%, the weight thereof increased by 12 to 13%, namely the sodium salt shows a remarkably high hygroscopicity.
The above-mentioned facts show that when the Ara-C-5'-stearylphosphate sodium salt obtained by the publicly known process is prepared into a medical product, particular consideration of the hygroscopicity thereof should be given and also a strict packaging of the product is necessary to prevent the product from taking up water when the product is put into market. In addition to the above, since the Ara-C-5'-stearylphosphate sodium salt is poor in stability and the activity in the preparation including the compound as an active ingredient is reduced by the decomposition in very short time, such a preparation cannot be actually put into market.
As a result of the present inventors' studies for providing a novel process for producing Ara-C-5'-stearylphosphate monosodium salt which is stable and suitable for producing medicines, it has been found by the present inventors that a stable Ara-C-5'-stearylphosphate monosodium salt can be obtained by adjusting an aqueous solution or suspension of Ara-C-5'-stearylphosphate to pH 9.7 to 13 by sodium hydroxide and further that by transforming the thus obtained monosodium salt into Ara-C-5'-stearylphosphate monosodium salt monohydrate represented by the following formula: ##STR1## under a specified condition, it can be possible to obtain a compound which is nonhygroscopic and is excellent in stability.
On the basis of the findings, the present inventors have completed the present invention.